Cell Membrane and Cell Polarity Flashcards
Part of the plasma membrane which creates a barrier to most water soluble molecules
Lipids
Make up roughly 30% of the genome
Transmembrane proteins
The lipid and protein interactions in the plasma membrane are
Non-covalent
Proteins and lipids can often move in the
Bilayer
What are the four classes of membrane lipids?
- ) Phosphoglycerides
- ) Sphingolipids
- ) Glycolipids
- ) Sterols
Derived from 3-carbon glycerol backbone with 2 fatty acid chains attached to backbone
-There are three major types
Phosphoglycerides
Derived from sphingosine backbones
-Sphingomyelin is a major one
Sphingolipids
Often a sphingosene backbone with carbohydrates on the external face
Glycolipids
The four major classes of membrane lipids make up what percentage of the membrane mass?
50%
Their structure allows them to assemble into a bilayer which insulates the cell from the environment
Lipids
Amphipathic membrane lipids assemble spontaneously
into lipid bilayers and then into
Liposomes
Lipids in solution will first form a bilayer, with hydrophobic regions insulated from water, then free edges will associate to form a
Liposome
One chain lipids in solution will form
Micelles
What is the basic structure of a phosphoglyceride?
head group, then a phosphate, glycerol, and 2 hydrocarbon tails
Two fatty acid chains attach to two of the three carbons of the
Glycerol backbone
Importantly, one of the two chains is typically
-opposes dense packing and leads to membrane fluidity
Unsaturated (has a double bond)
The three major phospholipid groups of the plasma membrane are named according to their head groups. What are they?
- ) Phosphatidyl Ethanolamine
- ) Phosphatidyl Serine
- ) Phosphatidyl Choline
Has a net negative charge
Phosphatidyl Serine
What are the five major lipids of the plasma membrane?
- ) Phosphatidyl Ethanolamine
- ) Phosphatidyl Serine
- ) Phosphatidyl Choline
- ) Sphingomyelin
- ) Sphingosine
Stiffens regions of the plasma membrane in its vicinity
-found in both leaflets of plasma membrane
Cholesterol
Its aliphatic regions keep phospholipid chains apart
Cholesterol
How many types of glycolipids are there?
40 types
Charged glycolipids
Gangliosides
Derived from sphingosine but have sugars added rather than phosphate
Glyclipids
Asymmetric, meaning that their sugar is present only on the external face of the plasma membrane
Glycolipids
GM1 ganglioside is used for entry of
Cholera toxin
Lipid composition of specific membranes can vary by both membrane type and
Cell type
Primarily located in plasma membranes (less internal)
Cholesterol and sphingomeylin
Enriched in intracellular membranes such as in mitochondria or endoplasmic reticulum
Phosphatidylethanolamine and phosphatidylcholine
Located in the plasma membrane and enriched in meylin, but there are little in the internal membranes
Glycolipids
Lipids laterally diffuse in both inner and outer
layers but rarely
Flip between leaflets
Absent from bacteria and plants
Cholesterol
Subdomains of the plasma membrane that contain high concentrations of cholesterol and glycosphingolipids. They exist as distinct liquid-ordered regions of the membrane that are resistant to extraction with nonionic detergents
Lipid rafts
Plasma membrane lipids are asymmetrically distributed between
Internal and external faces
Which lipids typically make up the inner leaflet?
Phosphatidylethanolamine and phosphatidyl serine
Which lipids typically make up the outer leaflet?
Sphingolipids, glycolipids, and phosphotidylcholine
Areas of non-random lipid distribution within inner or outer membrane leaflet
Lipid Rafts
Lipids can non-randomly associate in “rafts” enriched in cholesterol and sphingomeylin. They can sequester subsets of
Membrane proteins
There are many thousands of
Minor lipids
An example of a “minor” lipid that is now known to have amajor role in signaling
Phosphotidylinositol (PI)
Phosphotidylinositol serves as a dock for downstream signaling molecules and is a precursor to soluble
IP3
Membrane proteins can be either
Integral or Peripheral
Incorporated into membrane with stretches of hydrophobic amino acids that are arranged in either alpha helices of 15-20 aa or barrels, with hydrophilic aa buried
Integral membrane proteins
Some “integral” proteins have a lipid covalently attached that can reversibly interact with the
-Are not true integral proteins
Membrane
Usually associate with the membrane through non-covalent interactions (like electrostatic interactions)
Peripheral membrane proteins
Serve as signaling molecule, adhesion, receptors, and transport
Membrane proteins
Proteins can be post-translationally bound to several types of lipids that then mediate association with the
Membrane
Membrane proteins can be immobilized by the underlying
Cytoskeleton
Membrane proteins often diffuse within the membrane
but can be anchored to
Cytoskeleton
Cytoskeletal protein spectrin is a dimer attached indirectly (via intermediates) to the transmembrane proteins
Glycophorin and/or band 3
Create a barrier to transport of many molecules, especially ions and small molecules
Membrane lipids
What are the three distinct types of molecules that serve as transporters across the membrane?
- ) Pumps
- ) Carriers
- ) Channels
Moves ions/molecules uphill, or against the gradient, and into or out of the cell
-highly specific
Pumps
Pumps require
Energy
Have an intermediate specificity and serve to help molecules/ions to move down their gradients (downhill) into/out of the cell
Carriers
Do carriers require energy input?
No
Not very specific and serve to allow molecules to freely flow down their gradients without physically helping them
Channels
Do channels require energy?
No
Of the three transporters, which is the only one that can transport multiple ions per conformational change?
Channel
Many disease states result from alterations in the levels or structure of
Transporters
Channels and carriers are considered to be
Passive transport
Ion-specific pores that open and close in a regulated manner
Channels
Enzyme-like proteins that mediate passive transport down concentration gradients without chemical change
Carriers
Enzymes that need energy to move ions and other solutes across the membrane against a concentration gradient; energy provided via ATP mediated phosphorylation or ATP binding and hydrolysis
Pumps
Can promote or oppose ion movements driven by concentration gradients
-combine to produce electrochemical gradient
Membrane potential
Regulation of pore opening (open/closed) alters ion flow and rejects inappropriate ion because of
Charge or Size
Which two things block sodium channels
Tetrodoxin and lidocaine
What are two potassium channel blockers?
Scorpion venum and cone snail toxins
What are the three major “carrier-type” transporters
Uniport, symport, and antiport
Carrier that allows passive transport down the concentration gradient
Uniport
Coupled transport where the transport of one solute depends on the transport of another
Symport (same direction) and Antiport (opposite directions)
In an antiport, the free energy release from a molecule moving down its concentration gradient can be used to
Drive the second transport step
Undergo a random switch between states that sequentially open on both membrane sides whether or not solute is bound
-The end result is that solutes will move down concentration gradient at higher rate than by diffusion
Uniport Carrier transporters
Carrier transporters will depend on concentration gradient and binding affinity similar to
Enzyme kinetics
What is an example of a coupled carrier transporter?
Na-Glucose symporter
Displays co-operative binding such that binding of Na+
increases affinity of symporter for glucose
Na-Glucose symporter
Allows transport of glucose against concentration gradient without direct energy expenditure
-both sites need to be occupied for conformational switch to occur
Na-Glucose symporter
Transcellular glucose transport from digestive system
through epithelial cell uses two
Glucose transporters
The first step in moving glucose through epithelial cells is that Na+ moves down its gradient which
Drags glucose inside (Na-Glucose symporter)
The second step in moving glucose through epithelial cells is that once inside the epithelial cell, glucose moves down its gradient through a
Different transporter
To keep the system working properly, epithelial cells get rid of the sodium brought in with glucose using a
-ATP dependent pump
Na/K transporter on basal surface
What are the three classes of ATP driven pumps?
- ) P-type
- ) F-type (and V-type)
- ) ABC transporter
Multi-pass TM domains that autophosphorylate themselves resulting in a conformational change that pumps ions
P-type pump
Has multiple subunits that uses H+ flux to drive ATP synthesis
-Also used to acidify vesicles
F-type (and V-type) pump
ATP-driven pump that pumps small molecules rather than ions
ABC transporter
One of the most important P-type transporters that keeps the Ca2+ concentration low in the cytosol
Ca2+ ATPase
Makes up 90% of membrane protein in muscle cells
Ca2+ ATPase
How does the Ca2+ TPase work?
Ca2+ binds non-phosphorylated transporter. This allows ATP to bind and phosphorylate the transporter which induces a conformational change that opens the channel to the lumen of the sarcoplasmic reticulum (SR) and releases Ca2+
Another important P-type phosphorylator that uses 1/3 of the cellular energy
Na/K ATPase
How does the Na/K ATPase work?
Na+ binds, phosphorylation induces conformational change that releases and allows K+ to bind. Dephosphorylation then induces another conformational change and K+ is released
What is the net movement of the Na/K ATPase?
Moves 3 Na+ out and 2 K+ in
Have two ATPase domains in each, and small molecules bind to the non-ATP bound state
-Abundant: can be 5% of genes in bacteria
ATP-binding-casettes (ABC transporters)
In an ABC transporter, when ATP is bound, the two ATPase domains dimerize, which produces a conformational change that
Exposes substrate to the opposite side of the membrane
ATP hydrolysis then releases the
Substrate
There are over 100 of these in humans and they are clinically important
ABC transporters
In multiple drug resistance (MDR), high levels of one type of ABC transporter can arise in tumor cells, which allows more hydrophobic drug to be cleared from cytoplasm so that
-occurs in 40% of cancers
Drug effects are reduced
ATP binding to cystic fibrosis TM conductance regulator protein (CFTR) drives opening and closing of a
Cl- channel (and ABC transporter)
Binds to acetylcholine receptor (Ach) and blocks nerve transmission
Curare
